Development and Characterization of a Rapid-Onset Rodent Inhalation Model of Asbestosis for Disease Prevention

Mossman, Brooke T.; Janssen, Yvonne M. W.; Marsh, Joanne P.; Sesko, Ann; Shatos, Marie A.; Doherty, Jacqueline M.; Adler, Kenneth B.; Hemenway, David R.; Mickey, Ruth M.; Vacek, Pamela M.; Petruska, Janet; Kagan, Elliott

doi:10.1177/0192623391019004-110

Cited by 12 publications

(5 citation statements)

References 26 publications

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“…Furthermore, crocidolite fibers have been shown to induce the formation of the potentially carcinogenic modified DNA base, 8-hydroxy-2 Ј -deoxyguanosine, in A549 human lung epithelial cells via an · NO-dependent pathway (15). In this study, using a defined in vivo model of prefibrotic, asbestos-induced injury in the rat (7,16), we show for the first time that inhalation of asbestos fibers stimulates the production of RNS in the lungs and pleura. Furthermore, we demonstrate that chrysotile as well as crocidolite asbestos fibers can induce the formation of nitrotyrosine, a marker of ONOO Ϫ produc-tion, at sites of asbestos fiber deposition as well as in the airway epithelium and pleural mesothelium.…”

Section: Introductionmentioning

confidence: 63%

“…The rats in each group were comparably matched for age (56 d old) and size (mean weight for each group: 207 g) before inhalation exposure. Using an established inhalation exposure protocol (7,16,17), each group was exposed for 6 h/d on 5 d/wk over 2 wk. The rats were killed at 1 or 6 wk after the cessation of exposure by the intraperitoneal administration of sodium pentobarbital (50 mg/kg), followed by exsanguination via the abdominal aorta.…”

Section: Methodsmentioning

confidence: 99%

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Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat.

Tanaka

Choe²,

Hemenway³

et al. 1998

J. Clin. Invest.

106

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To determine whether asbestos inhalation induces the formation of reactive nitrogen species, three groups of rats were exposed intermittently over 2 wk to either filtered room air (sham-exposed) or to chrysotile or crocidolite asbestos fibers. The rats were killed at 1 or 6 wk after exposure. At 1 wk, significantly greater numbers of alveolar and pleural macrophages from asbestos-exposed rats than from sham-exposed rats demonstrated inducible nitric oxide synthase protein immunoreactivity. Alveolar macrophages from asbestos-exposed rats also generated significantly greater nitrite formation than did macrophages from shamexposed rats. Strong immunoreactivity for nitrotyrosine, a marker of peroxynitrite formation, was evident in lungs from chrysotile-and crocidolite-exposed rats at 1 and 6 wk. Staining was most evident at alveolar duct bifurcations and within bronchiolar epithelium, alveolar macrophages, and the visceral and parietal pleural mesothelium. Lungs from sham-exposed rats demonstrated minimal immunoreactivity for nitrotyrosine. Significantly greater quantities of nitrotyrosine were detected by ELISA in lung extracts from asbestos-exposed rats than from sham-exposed rats. These findings suggest that asbestos inhalation can induce inducible nitric oxide synthase activation and peroxynitrite formation in vivo, and provide evidence of a possible alternative mechanism of asbestos-induced injury to that thought to be induced by

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Section: Introductionmentioning

confidence: 63%

Section: Methodsmentioning

confidence: 99%

Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat.

Tanaka

Choe²,

Hemenway³

et al. 1998

J. Clin. Invest.

106

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“…A number of environmental dust and fiber exposures have been associated with the development of lung fibrosis (137). Both silica and asbestos exposures produce lung fibrosis in animals (64,104) and pneumoconiosis in humans (164).…”

Section: Fibrogenic Environmental Agents and Oxidative Stressmentioning

confidence: 99%

Antioxidants as Potential Therapeutics for Lung Fibrosis

Day

2008

Antioxidants & Redox Signaling

125

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Interstitial lung disease encompasses a large group of chronic lung disorders associated with excessive tissue remodeling, scarring, and fibrosis. The evidence of a redox imbalance in lung fibrosis is substantial, and the rationale for testing antioxidants as potential new therapeutics for lung fibrosis is appealing. Current animal models of lung fibrosis have clear involvement of ROS in their pathogenesis. New classes of antioxidant agents divided into catalytic antioxidant mimetics and antioxidant scavengers are being developed. The catalytic antioxidant class is based on endogenous antioxidant enzymes and includes the manganese-containing macrocyclics, porphyrins, salens, and the non-metal-containing nitroxides. The antioxidant scavenging class is based on endogenous antioxidant molecules and includes the vitamin E analogues, thiols, lazaroids, and polyphenolic agents. Numerous studies have shown oxidative stress to be associated with many interstitial lung diseases and that these agents are effective in attenuating fibroproliferative responses in the lung of animals and humans.

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“…Asbestos mineral samples were obtained from the National Institute of Environmental Health Sciences (NIEHS; Research Triangle Park, NC). These samples have been characterized previously (14), and have been shown to be fibrogenic to rats in vivo (26,27) and to induce a pleural macrophage inflammatory response in a rat inhalation model (5). Carbonyl iron spheres (size range: Ͻ 1 to 10 m; average particle size: 4.5 to 5.2 m) were purchased from Sigma Chemical Co. (St. Louis, MO).…”

Section: Mineral Samples and Reagentsmentioning

confidence: 99%

Asbestos Fibers and Interleukin-1 Upregulate the Formation of Reactive Nitrogen Species in Rat Pleural Mesothelial Cells

Choe

Tanaka

Kagan

1998

Am J Respir Cell Mol Biol

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Nitric oxide radical (.NO) and peroxynitrite anion (ONOO-) have been implicated in lung inflammation and may be important in pleural injury. The present study was undertaken to determine the effects of asbestos exposure and cytokine stimulation on .NO and ONOO- production by rat pleural mesothelial cells. Accordingly, rat parietal pleural mesothelial cells were cultured for 2 to 72 h with or without 50 ng/ml of recombinant interleukin-1beta (IL-1beta) in the presence (1.05 to 8.4 microg/cm2) or absence of crocidolite or chrysotile asbestos fibers. The effects of asbestos were compared with those of carbonyl iron, a nonfibrogenic particulate. Mesothelial cell messenger RNA (mRNA) expression of the inducible form of .NO synthase (iNOS), assessed with the reverse transcription-polymerase chain reaction (RT-PCR), increased progressively from 2 to 12 h in IL-1beta-containing cultures. Nitrite (NO2-), the stable oxidation product of .NO in mesothelial cell conditioned medium, was assayed through the Griess reaction. Both types of asbestos fibers (chrysotile > crocidolite) upregulated the formation of NO2- in mesothelial cells costimulated with IL-1beta in a concentration-dependent and time-dependent fashion. In contrast, carbonyl iron did not upregulate NO2- formation in IL-1beta-stimulated cells. Both types of asbestos fibers also induced iNOS protein expression and the formation of nitrotyrosine in mesothelial cells and greatly induced the formation of nitrate (NO3-), a surrogate marker of ONOO- formation, in IL-1beta-stimulated cells. However, the effects of chrysotile were notably greater than those of crocidolite. These findings may have significance for the induction of pleural injury by asbestos fibers.

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Development and Characterization of a Rapid-Onset Rodent Inhalation Model of Asbestosis for Disease Prevention

Cited by 12 publications

References 26 publications

Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat.

Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat.

Antioxidants as Potential Therapeutics for Lung Fibrosis

Asbestos Fibers and Interleukin-1 Upregulate the Formation of Reactive Nitrogen Species in Rat Pleural Mesothelial Cells

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